Pfizer’s oral JAK inhibitor candidate tasocitinib (CP-690,550) significantly reduced the signs and symptoms of moderately to severely active rheumatoid arthritis (RA), according to new Phase III trial data. The Oral Solo (1045) study showed that in comparison with placebo, tasocitinib monotherapy also led to improvements in physical function at three months, as measured by ACR20 response rates and mean change in HAQ-DI (Health Assessment Questionnaire Disability Index). In addition to the positive Oral Solo trial data, results from the ongoing Phase II/III open-label follow-up study, Oral Sequel (1024), confirmed the benefits of tasocitinib either as monotherapy or in combination with methotrexate, after 24 months.
The Oral Solo Phase III study enrolled 611 patients with moderately to severely active RA who had demonstrated inadequate response to at least one disease-modifying antirheumatic drug (DMARD). Patients were randomized to receive tasocitinib 5 mg or 10 mg therapy administered twice daily, or placebo. After the first three months patients who had received placebo were also switched to tasocitinib 5 mg or 10 mg therapy.
The results showed that after three months, 59.8% of patients receiving 5 mg tasocitinib twice daily and 65.7% of those on the 10 mg dose achieved an ACR20 response rate (i.e., a 20% improvement from baseline in the American College of Rheumatology scale). This compared with just 26.7% of placebo patients. ACR50 response rates were 31.1% and 36.8%, respectively, for the 5 mg and 10 mg tasocitinib cohorts, and 12.5% for placebo patients. The three respective ACR70 response rates were 15.4%, 20.3%, and 5.8%. Mean changes from baseline for HAQ-DI scores were -0.5 and -0.57 for patients receiving the lower and higher tasocitinib doses, and -0.19 for placebo patients.
The Phase III program for tasocitinib in RA includes six trials with over 350 locations in some 35 countries. Oral tasocitinib is also being evaluated against diseases including psoriasis, inflammatory bowel disease (Crohn disease and ulcerative colitis), and organ transplantation. Topical tasocitinib is being evaluated both for the treatment of dry eye and psoriasis.